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<p>Developing a vaccine that can both elicit robust antitumor immune responses and exert potent tumoricidal effects remains a formidable challenge. Herein, we design a functional dendrimer nanocarrier to co-deliver manganese dioxide (MnO<sub>2</sub>) nanoparticles (NPs) and ovalbumin peptide antigen OVA<sub>257−264</sub> for synergistic tumor chemodynamic/immunotherapy and tumor prevention. Specifically, generation 5 (G5) poly(amidoamine) dendrimers functionalized with methoxy poly(ethylene glycol) (<i>m</i>PEG) and heptafluorobutyric acid (HFBA) were used to entrap MnO<sub>2</sub> NPs with an average size of 2.6&#xa0;nm and complex OVA<sub>257−264</sub>. The ultimately constructed MnO<sub>2</sub>@G5-<i>m</i>PEG-HFBA/OVA<sub>257−264</sub> (MGPF/OVA<sub>257−264</sub>) NPs respond to tumor microenvironment for rapid release of Mn<sup>2+</sup> that can catalyze a Fenton-like reaction to initiate chemodynamic therapy (CDT) for tumor cell immunogenic cell death (ICD) induction and promote tumor-associated macrophage M1 polarization. The generated ICD combined with Mn²⁺-mediated stimulator of interferon genes (STING) pathway activation can synergize the co-delivered OVA<sub>257−264</sub> antigen to facilitate maturation of dendritic cells for cross-presentation of antigens. In a mouse subcutaneous colorectal cancer model, the MGPF/OVA<sub>257−264</sub> nanovaccine exhibits potent therapeutic and prophylactic efficacy, markedly suppressing tumor growth and recurrence through CDT cytocidal effect and robust immune activation. The developed dendrimer-based theranostic peptide nanovaccine may be extended to tackle other types of solid tumors through cooperatively potentiating antitumor immune responses.</p> Graphical Abstract <p></p>

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Manganese dioxide-entrapping dendrimers as a therapeutic peptide vaccine for combined tumor chemodynamic/immune therapy and tumor prevention

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月31日

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  • Lili Xia,
  • Jinxia Wang,
  • Aiyu Li,
  • Yanying Li,
  • Jiahui Liu,
  • Xiangyang Shi,
  • Mingwu Shen

摘要

Developing a vaccine that can both elicit robust antitumor immune responses and exert potent tumoricidal effects remains a formidable challenge. Herein, we design a functional dendrimer nanocarrier to co-deliver manganese dioxide (MnO2) nanoparticles (NPs) and ovalbumin peptide antigen OVA257−264 for synergistic tumor chemodynamic/immunotherapy and tumor prevention. Specifically, generation 5 (G5) poly(amidoamine) dendrimers functionalized with methoxy poly(ethylene glycol) (mPEG) and heptafluorobutyric acid (HFBA) were used to entrap MnO2 NPs with an average size of 2.6 nm and complex OVA257−264. The ultimately constructed MnO2@G5-mPEG-HFBA/OVA257−264 (MGPF/OVA257−264) NPs respond to tumor microenvironment for rapid release of Mn2+ that can catalyze a Fenton-like reaction to initiate chemodynamic therapy (CDT) for tumor cell immunogenic cell death (ICD) induction and promote tumor-associated macrophage M1 polarization. The generated ICD combined with Mn²⁺-mediated stimulator of interferon genes (STING) pathway activation can synergize the co-delivered OVA257−264 antigen to facilitate maturation of dendritic cells for cross-presentation of antigens. In a mouse subcutaneous colorectal cancer model, the MGPF/OVA257−264 nanovaccine exhibits potent therapeutic and prophylactic efficacy, markedly suppressing tumor growth and recurrence through CDT cytocidal effect and robust immune activation. The developed dendrimer-based theranostic peptide nanovaccine may be extended to tackle other types of solid tumors through cooperatively potentiating antitumor immune responses.

Graphical Abstract